With an increasingly aging and stressed society, the number of patients with lower urinary tract dysfunction (LUTD) has increased. LUTD is a generic term for urine collection disorder and dysuria, and the symptoms derived from LUTD are lower urinary tract symptoms (LUTS). One of the LUTS is an overactive bladder syndrome (OABs). OABs may also be generally called overactive bladder (OAB). In any case, it is a disease defined as “a symptom syndrome which essentially has urinary urgency and which is usually accompanied by urinary frequency and nocturia. Urge urinary incontinence is not necessary”. The symptoms associated with OABs interfere with general life activities such as work, daily life, mental activity, and the like, and thus lower the quality of life (QOL). Currently, the first choice drug as an agent for treating OABs is an anticholinergic agent. However, it is necessary for the anticholinergic agent to be used upon sufficient consideration of an anti-muscarinic effect such as thirst and residual urine, and thus the anticholinergic agent is not always effective for all patients (see, for example, Non-patent literature 1). Under these circumstances, there is a demand for development of a therapeutic agent which has a different mechanism from that of the anticholinergic agent (see, for example, Non-patent literature 1).
Recently, in LUTS, particularly in OABs, the role of urothelium has attracted attention. For LUTS, it has become clear that various chemical mediators are released in the urothelial cells, which cause a micturition reflex through the receptors of bladder sensory nerve terminals. Among them, one of the chemical mediators, prostaglandin E2 (PGE2), binds with a prostaglandin E receptor 1 (EP1 receptor) in the afferent nerves (especially C fibers) in the urothelium to increase the micturition reflex. In addition, PGE2 binds with the EP1 receptor present in the bladder smooth muscle to contract the bladder. In fact, it has been reported that the EP1 receptor antagonists inhibit both of the increase in the micturition reflex and the increase in the afferent nerve activities by PGE2 (see, for example, Non-patent literature 2 and Non-patent literature 3). Given the above, it is suggested that PGE2 is involved in contraction of the bladder smooth muscle and increase in the bladder sensory nerves through the EP1 receptors. Furthermore, it is reported that the EP1 receptor antagonists do not increase the amount of the residual urine, but increase the bladder capacity (see, for example, Non-patent literature 4).
There exist four subtypes of the PGE2 receptor: EP2, EP3, and EP4 as well as EP1. The EP1 receptor exists in the lungs as well as the bladder and the urothelium, the skeletal muscle, the renal collecting duct, and the like (see, for example, Non-patent literature 2). Therefore, it is expected that by changing the selectivity of the subtypes of the PGE2 receptor, the target organs of the drugs, or the target tissues, a therapeutic agent for desired diseases can be developed.
As an indole in which the 1-, 2-, and 5-positions are substituted, N,N-dimethyl-1-{[4-(5-methoxy-2-phenyl-1H-indol-1-yl)methyl]benzoyl}pyrrolidin-3-ylamine represented by the chemical structural formula (A), which is an H3 receptor inhibitor, and the like have been described (see, for example, Patent literature 1).

Further, a compound represented by the general formula (B) having an angiotensin II receptor inhibitory effect has been disclosed (see, for example, Non-patent literature 5).

In the formula B, Ra represents a hydrogen atom or a fluorine atom, and Rb represents a hydrogen atom or a chlorine atom.
However, the chemical structures of these compounds are different from the chemical structure of the compound of the present invention. Further, it is not described or suggested that these compounds have a prostaglandin EP1 receptor antagonism.
A compound represented by the chemical structural formula (C) and the like have been described as an indole derivative having an EP1 receptor antagonism (see, for example, Patent literature 2)

However, the chemical structure formulae of these compounds are different from the chemical structure formula of the compound of the present invention with respect to the positions, types, and the like of the substituents.
International Publication WO 2007/108936 pamphlet.
International Publication WO 2008/006790 pamphlet.
Narihito Seki, Folia Pharmacologica Japonica, 2007, Vol. 129, p. 368-373.
Xiaojun Wang, et al., Biomedical Research, 2008, Vol. 29, p. 105-111.
Masahito Kawatani, PAIN RESEARCH, 2004, Vol. 19, p. 185-190.
Masanobu Maegawa, The Journal of The Japan Neurogenic Bladder Society, 2008, Vol. 19, p. 169.
Richard D. Cramer, et al., Journal of Medicinal Chemistry, 1999, Vol. 42, p. 3919-3933.